Many cytokines are known as humoral factors involved in the growth and differentiation of various types of cells, or in the activation of differentiated mature cell functions. Cytokine-stimulated cells produce different types of cytokines, thereby forming networks of multiple cytokines in the body. Biological homeostasis is maintained by a delicate balance of the mutual regulation between cytokines in these networks. Many inflammatory diseases are thought to result from a failure of such cytokine networks. Thus, monoclonal antibody-based anti-cytokine therapy is drawing much attention. For example, anti-TNF antibodies and anti-IL-6 receptor antibodies have been demonstrated to be highly effective clinically. On the other hand, there are many examples of failure where no therapeutic effects were produced when a single cytokine, such as IL-4, was blocked alone, due to the activation of compensatory pathways in actual pathological conditions.
The present inventors succeeded in isolating a novel cytokine receptor NR 10 that was highly homologous to gp130, a receptor for IL-6 signal transduction (Patent Document 1). NR 10 forms a heterodimer with oncostatin M receptor (OSMR) and functions as an IL-31 receptor (Non-patent Document 1). Zymogenetics, Inc. reported that transgenic mice overexpressing IL-31 spontaneously developed pruritic dermatitis (Patent Document 2).
However, it cannot be asserted that the forced expression of a cytokine in mice or a high blood level of a cytokine in pathological model mice is indeed the cause of a disease. There is no information on whether any therapeutic effects are produced when a signal is blocked by an antibody. For example, pruritic dermatitis develops in transgenic mice in which IL-18 is overexpressed in keratinocytes. Furthermore, the blood IL-18 concentration elevates with the progression of pathological conditions in NC/Nga model mice for spontaneous atopic dermatitis. Based on the above findings, the overexpression of IL-18 was predicted to be the cause of disease. In reality however, the administration of neutralizing antibodies produced no therapeutic effects (Non-patent Document 2).
As described above, inhibition of the function of a cytokine does not necessarily produce therapeutic effects in diseases in which the expression level of a cytokine is elevated. Prediction of diseases on which therapeutic effects are actually produced is difficult to make based on the expression level of a cytokine. It is thus important to find diseases in which inhibition of signal transduction of a target cytokine actually produces therapeutic effects.
Prior art documents of the present invention are described below.    Patent Document 1: WO 00/75314    Patent Document 2: WO 03/060090    Non-patent Document 1: IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis, J Allergy Clin Immunol. 2006 February; 117(2): 418-25    Non-patent Document 2: Administration of anti-interleukin 18 antibody fails to inhibit development of dermatitis in atopic dermatitis-model mice NC/Nga, British Journal of Dermatology 149: 39-45, 2003